T lymphocytes can mediate and regulate both the specific and non-specific effector mechanisms of immune responses. CD4+ T lymphocytes provide help for antibody production and secrete cytokines which modulate the growth of other T cells and the growth and differentiation of other immune cells such as monocytes and granulocytes. Functional and biochemical studies have demonstrated that the generation of cellular immune responses depends upon antigen receptors on T cells that recognize peptide fragments of foreign proteins associated with products of the major histocompatibility complex (MHC) that are expressed on antigen-presenting accessory cells. Recent advances in technology have made it possible to culture efficiently antigen-specific human and mouse T cell lines and clones in vitro. In addition, it is now possible to produce large amounts of protein antigens or their fragments using recombinant DNA technology or solid phase peptide synthesis. Thus, in the last few years, several research groups have begun to determine the linear amino acid sequences of antigenic proteins that are recognized by T cells in association with MHC (T cell epitopes).
Peptides derived from a variety of protein antigens, including bacterial and viral pathogens, autoantigens, allergens and other experimental antigens such as hen egg lysozyme (HEL), ovalbumin (OVA) and lambda repressor (cl) have been examined for the ability to stimulate antigen-specific T cells. A wide size spectrum of peptides has been reported to serve as T cell epitopes. For example, OVA amino acid residues 324–339 (Shimonkevitz, R. et al., J. Immunol., 133:2167 (1984)), HEL amino acid residues 74–96 (Shastri, N. et al., J. Exp. Med. 164:882–896 (1986); and lambda repressor (cl) amino acid residues 12–26 (Lai, M.-Z et al., J. Immunol., 139:3973–3980 (1987)) have been demonstrated to trigger efficiently whole protein-primed T cells. A peptide derived from Hepatitis B surface antigen (HBsAg amino acid residues 19–33) has recently been shown to stimulate T cell responses in a majority of human subjects who had been immunized with a recombinant hepatitis B vaccine (Schad, V. C. et al., Seminars in Immunol., 3:217–224 (1991)). A major mycobacterial antigen 65-kD protein has also been epitope-mapped (Lamb, J. R. et al., EMBO J., 6(5):1245–1249 (1987)). T cell epitopes have been identified in the peptides comprised of amino acid residues 112–132 and 437–459 of the 65-kD protein. Myelin basic protein (MBP), an autoantigen which induces experimental autoimmune encephalomyelitis (EAE) and the presumed autoantigen in multiple sclerosis (MS) has also been epitope-mapped in both human (Ota, K. et al., Nature, 346:183–187 (1990)) and rodent (Zamvil et al., Nature 324:258–260(1986)) systems. Ota et al. have identified a major T cell epitope recognized by MS patients, MBP amino acid residues 84–102. Minor epitopes (MBP amino acid residues 143–168, 61–82, 124–42 and 31–50) recognized by T cells from MS patients were also described. Zamvil et al. have shown that MBP amino acid residues 1–11 contain the major T cell epitope(s) causing EAE, in susceptible rodent strains.
T cell epitopes present in allergenic proteins have very recently been described (O'Hehir, R. et al., Ann. Rev. Immunol., 9:67–95 (1991)). Several peptides derived from the house dust mite allergen Der p I have been shown to be T cell-reactive (Thomas, W. R., et al. In Epitopes of Atopic Allergens Proceedings of Workshop from XIV Congress of the European Academy of Allergy and Clinical Immunology, Berlin (September 1989) pp. 77–82; O'Hehir, R. E. Annual Review Immunology 9:67–95 (1991); Stewart, G. A. et al In: Epitopes of Atopic Allergens Proceedings of Workshop from XIV Congress of the European Academy of Allergy and Clinical Immunology, Berlin (September 1989) pp 41–47; and Yessel, H. et al. In: T Cell Activation in Health and Disease: Discrimination Between Immunity and Tolerance, Conference 22–26 (September 1990) Trinity College, Oxford U.K.). A T cell-stimulatory peptide derived from the short ragweed allergen Amb a I amino acid residues 54–65 has also been reported (Rothbard, J. B. et al., Cell, 52: 515–523 (1988). Using a panel of T cell clones derived from a rye grass-allergic individual, Perez et al. demonstrated that T cell epitopes are contained within amino acid residues 191–210 of the protein allergen Lol p I (Perez, M. et al., J. Biol. Chem., 265(27):16210–16215 (1990)).